Journal Article

DZNE-2026-01103

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Tau isoform mapping across tissues and biofluids reveals a signature distinguishing Alzheimer's disease from amyotrophic lateral sclerosis.

Abu-Rumeileh, S. ; Großkopf, H. ; Guthknecht, A. ; Mensch, A. ; Osterloh, D. ; Ratti, A. ; Conrad, J. ; Stapf, C. ; Krippner, J. ; Oeckl, P.DZNE* ; Stoltenburg-Didinger, G. ; Maranzano, A. ; Steinacker, P. ; Weise, C. M. ; Barba, L. ; D'Anna, L. ; Klafki, H.-W. ; Wiltfang, J.Extern* ; Silani, V. ; Froelich, L. ; Ticozzi, N. ; Hausner, L. ; Thal, D. R. ; Weishaupt, J. H. ; Lachmann, I. ; Verde, F. ; Otto, M.

2026
Springer Nature [London]

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Please use a persistent id in citations: doi:10.1038/s41467-026-78390-3

Abstract: Blood phosphorylated tau 217 (p-tau217) accurately detects Alzheimer's disease (AD) pathology but is also elevated in amyotrophic lateral sclerosis (ALS), likely reflecting peripheral (big) tau released from muscle. Assays selectively measuring brain-derived (BD-) tau and BD-p-tau217 are therefore needed. We analysed serum BD-tau and p-tau217 in ALS (n = 139), AD (n = 101) and controls (n = 75) using direct immunoassays and after BD-Tau immunoprecipitation (BD-Tau-IP), and tau species in brain (n = 16), spinal cord (n = 11) and muscle (n = 10) by targeted mass spectrometry. With the direct immunoassays, BD-tau and p-tau217 were increased in AD and ALS versus controls. After BD-Tau-IP, BD-tau and BD-p-tau217 were elevated in AD only, improving diagnostic accuracy. Mass spectrometry revealed a central-to-peripheral shift from BD-tau to big tau predominance, with exclusively big p-tau217 detected in muscle. Selective detection of BD-tau species improves the specificity of blood AD biomarkers by reducing peripheral tau confounding.

Keyword(s): Humans (MeSH) ; Amyotrophic Lateral Sclerosis: diagnosis (MeSH) ; Amyotrophic Lateral Sclerosis: blood (MeSH) ; Amyotrophic Lateral Sclerosis: metabolism (MeSH) ; tau Proteins: blood (MeSH) ; tau Proteins: metabolism (MeSH) ; Alzheimer Disease: diagnosis (MeSH) ; Alzheimer Disease: blood (MeSH) ; Alzheimer Disease: metabolism (MeSH) ; Female (MeSH) ; Protein Isoforms: metabolism (MeSH) ; Protein Isoforms: blood (MeSH) ; Male (MeSH) ; Biomarkers: blood (MeSH) ; Biomarkers: metabolism (MeSH) ; Brain: metabolism (MeSH) ; Aged (MeSH) ; Phosphorylation (MeSH) ; Spinal Cord: metabolism (MeSH) ; Mass Spectrometry (MeSH) ; Middle Aged (MeSH) ; Diagnosis, Differential (MeSH) ; Aged, 80 and over (MeSH) ; Immunoprecipitation (MeSH) ; Case-Control Studies (MeSH) ; tau Proteins ; Protein Isoforms ; Biomarkers

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Contributing Institute(s):

1. Translational Mass Spectrometry and Biomarker Research (AG Öckl)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

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